Haemoglobinopathy Flashcards
describe the structure of a haemoglobin molecule
2 alpha globin chains
2 beta globin chains
one haem group (iron in porphyrin ring) per globin chain
what are the major forms of Hb
HbA (2 alpha, 2 beta)
HbA2 (2 alpha, to delta)
HbF (2 alpha, 2 gamma)
what is the most abundant type of haemoglobin in adults
HbA
what chromosome are the genes for alpha globins on and how many are there
chromosome 16
2 alpha genes per chromosome
4 alpha genes per cell
what chromosome are the genes for beta globins on and how many are there
chromosome 11
one beta gene per chromosome
2 genes per cell
when do we express HbF as opposed to HbA
HbF - foetal Hb
what are haemoglobinopathies
hereditary conditions affecting globin chain synthesis
haemoglobinopathies are generally dominant/recessive disorders
autosomal recessive
what is a thalassaemia
decreased rate of Hb synthesis (reduced or absent)
what happens in structural haemoglobin variant disorders
production of structurally abnormal globin chains
what are the 2 types of thalassaemias
alpha chain
beta chain
what type of anaemia do thalassaemias cause
microcytic hypochromatic
geographical risk factor for thalassaemia
tropical areas with high incidences of malaria
what does the imbalance of globin chain within red cells cause
ineffective erythropoiesis and premature red cell death
how many alpha genes are missing in a thal trait
one or two
how many alpha genes are missing in HbH disease
3
what is the condition where no functioning alpha genes
Hb Barts hydrops fetalis
how would you differentiate thalassaemia from iron deficiency
both would be microcytic anaemia (low Hb, low MCV)
thalassaemia has a normal ferritin level with raised red cell count)
clinical features of HbH disease
anaemia (possibly transfusion dependant)
splenomegaly
jaundice
management of HbH disease
splenectomy
potentially transfusion if required
clinical features of Hb Barts hydrops fetalis
severe anaemia cardiac failure growth retardation hepatosplenomegaly die in utero
how many faulty beta genes in B thalassaemia trait
one
how many faulty beta genes in thalassaemia intermedia
two genes causing reduced B chain production
OR
one gene causing reduced B chain production and one causing no B chain production
how many faulty beta chains in thalassaemia major
both genes causing no production of beta chains
presentation of thalassaemia major
6-24 months (when HbF falls off) pallor, failure to thrive hepatosplenomegaly skeletal changes organ damage
management of thalassaemia major
transfusion
monitor iron levels - prevent over-absorption
bone marrow transplant if before complications
consequences of iron overload
diabetes osteoporosis impaired growth cardiac disease liver disease
management of iron overload
iron chelating drugs - desferrioxamine
what causes sickle cell anaemia
point mutation on B globin gene causing HbS to be formed
what happens to HbS if exposed to low O2 sats
polymerises - distorts cell membrane
how many abnormal genes in sickle cell trait
1
how many abnormal beta genes in sickle cell anaemia
2
when may symptoms arise in sickle cell trait
severe hypoxia eg high altitude, under anaesthesia
what is sickle crisis
episodes of tissue infarction due to vascular occlusion
where is sickle crisis likely to occur
digits, bone marrow, lung, spleen, CNS
what are some consequences of sickle cell anaemia
chronic haemolysis
hyposplenism (from multiple splenic infarcts)
triggers of sickle crisis
hypoxia dehydration infection cold stress/disease
management of sickle crises
opiate analgesia hydration rest O2 antibiotics (in infection) red cell transfusion if severe (neurological symptoms, chest crisis)
long term management of sickle cell anaemia
reduce risk of infection - vaccines of encapsulated bacteria(pneumococcus, meningococcus, haemophilus) and prophylactic penicillin
folic acid
hydroxycarbamide (induces HbF production)
what are investigations needed to detect haemoglobinopathy
FBC, Hb, red cell indices
blood film
high performance liquid chromatography/gel electrophoresis (looks at quantities of different Hb)
what investigation is needed to confirm a thalassaemia trait
DNA testing
